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Objective: To determine the impact of variant histologic differentiation of patients with urothelial carcinoma of the bladder on survival after radical cystectomy.Methods: Between 2006 and 2012,418 consecutive patients who underwent radical cystectomy with lymphadenectomy for urothelial carcinoma of the bladder were included.The patients were divided into three groups based on pathological results: group A included 262 patients with pure urothelial carcinoma,group B included 103 patients with squamous and/or glandular differentiation and group C comprised 53 patients with non-squamous and/or glandular differentiation.The Kaplan-Meier method was used to estimate cancer-specific and overall survivals.Multivariate Cox proportional hazard regression analysis was used to evaluate the association of histological differentiation with cancer-specific and overall mortality.Results: Of the 418 patients,108 were diagnosed with a single variant histology,and 58 had multiple patterns.Squamous differentiation(n=48;11.5%)was the most common single variant histology,followed by glandular(n=40;9.6%)and sarcomatoid(n=13;3.1%).Compared to group A,group B and C were more likely to have advanced tumor stage(pT4 in group B vs.group C vs.group A: 29,14,24;28.2%vs.26.4%vs.9.2%),lymph node metastases(35,13,31;34.0%vs.24.5%vs.11.8%)and lymphovascular invasion(45,22,49;43.7%vs.41.5%vs.18.7%)(P values <0.017).In univariable analyses,group B and group C were at significantly higher risk for cancer specific mortality and overall mortality than patients with pure UCB(P values <0.01).In multivariable analyses,group C had significantly prognostic influence on cancer-specific mortality(HR 2.49,95%CI: 1.32-4.67,P<0.01)and overall mortality(HR 2.21,95%CI: 1.31-3.73,P<0.01).Conclusions: Variant differentiation was independently associated with adverse outcomes for patients with urothelial carcinoma of the bladder after radical cystectomy.